The benzodiazepines are potent anticonvulsant agents. These drugs may act by enhancing gamma amino butyric acid (GABA) - receptive neurons' responses to GABA. Binding sites to radioactive benzodiazepines have recently been identified in brain membranes. These binding sites may represent receptors which mediate the pharmacologic action of these drugs. We have demonstrated that repeated seizures cause an elevation of hippocampal benzodiazepine receptors 24 hours following the last seizure. A detailed understanding of this endogenous biochemical response to seizures may lead to improved pharmacologic approaches to the treatment of seizures. The specific goals of this proposal are: 1) to extend and elaborate our preliminary observation of seizure induced increases of hippocampal benzodiazepine receptors; 2) to localize the sites of the seizure induced benzodiazepine receptor increases within hippocampal formation, using correlative microdissection and autoradiographic techniques; and 3) to determine whether GABA receptors of hippocampal membranes are altered by seizures, and to characterize the regulation of benzodiazepine receptor binding by GABA following seizures. The hypothesis underlying these investigations is that the seizure induced increases of benzodiazepine receptors imply enhanced neuronal responsiveness to the benzodiazepines. Accomplishment of these specific objectives should provide valuable information for testing this hypothesis with correlative electrophysiologic studies of the in vitro hippocampal slice preparation.